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L0301P62 - Envenoming and the Neuromuscular Junction
Venomous Animals *spider - funnel web *octopus - blue ringed *fish - stonefish *jellyfish - box *snake - inland taipan All of which live in Australia Venomous *possess some form of venom apparatus *i.e. gland, specialised cells, duct, delivery mechanisms (sting, fang, spine) Poisonous *toxins but no apparatus *pufferfish - only cause harm when ingested Snakes Elapids *small fangs (2-5 mm long) *fangs cannot move *most Australian snakes Vipers ''' *large fangs (few cm) can move '''Colubrids *rear fangs *rarely bite and harm humans Snake Bites Australia *not a large medical problem *500 - 3000 bites a year **mostly dry bites - no venom in circulation **only 1:10 require antivenom **around 2 fatalities per year Worldwide ''' *plantation workers, famers and herdsmen *50,000-100,000 per year Signs and Symptoms of Snake Bite *partial ophthalmoplegia (paralysis of eye muscles) *ptosis - drooping of eyelids *double vision - diplopia *difficulty breathing *difficulty speaking (dysarthria) *loss of facial expression Systemic Spread Signs *pain on contracting muscles against resistance *muscle weakness (similar to paralysis) *dark urine (generally has blood) CSL Snake Venom Detection Kit (VDK) *rapid 25 min 2 step enzyme immunoassay which detects broad identity of the snake *swab from: **bite site **clothing **blood - not recommended due to false positives/negatives **urine *identify 5 major genera *depends on colour change in the wells **besides wells 6 and 7 which are controls Determining How Venomous *measured by lethality - LD50 **dose of venom that kills 50% of mice over a 24/48 hour period '''Venomous Snakes List #Inland taipan - 0.010 LD50 #Eastern brown snake - 0.041 #Coastal taipan - 0.064 #Common tiger snake - 0.118 Snake Venom *Aim: immobilise (kill); digest; defence *‘a mosaic of antigens’ *90-95% dry weight is protein *peptide toxins have evolved which affect vital processes of mammals Neurotoxin *affects release of transmitter (ACh) or binding of transmitter to receptors (nicotinic) Presynaptic Action - β-neurotoxins *elapids, vipers, crotalids (pit vipers) *stops recycling of vesicles for ACh *irreversible *slow onset *only responds to antivenom is given early **late = too much damage of nerve terminal Postsynaptic Action - α-neurotoxins *elapids and sea snakes only *“curare like” **blocks ACh binding to nAChR like a competitive antagonist *usually rapid onset *reversible *responds to anticholinesterases and antivenom Haemotoxins - Blood Coagulants Procoagulant Activity *widespread clot formation/defibrinogenation (venom-induced consumption coagulopathy) **run out of clotting factors *prothrombin activator —> prothrombin —> thrombin —> fibrinogen —> fibrin Anticoagulant Activity *less common in Australian snake venoms **common copperhead, death adder Treatment of Snake Bites *call poison information centre for advice *pressure immobilisation - Struan Sutherland *monovalent / polyvalent antivenoms (CSL) First Aid *pressure and immobilisation to stop flow of venom through limbs *bandage firmly over bitten area and above *bind splint firmly to the limb *may be maintained for several hours until antivenom is administered Antivenoms *purified antibodies (F(ab)2 fragments) obtained from animals immunised against the venom *i.e. animal ‘Blood Bank’ - usually horses Box Jellyfish *C.Fleckeri *grow up to 60 tentacles, bell size ~325mm *most venomous creature in the world *causes cardiac and respiratory failure Envenoming Process *tentacles and bells covered in sting cells *nematocysts (sting cells) *different types - isorhiza, mastigophores *deliver venom and/or adhere to the prey First Aid *remove victim from water *inactivate remaining tentacles using vinegar *monitor respiration and pulse (resuscitation) *antivenom (intravenous or intramuscular) *pressure/immobilisation not recommended Carukia Barnesi (Irukandji jellyfish) *small: bell size 1.5-2.5cm, tentacles: 1m *large distribution in northern Aus waters *can cause Irukandji Syndrome Irukandji Syndrome *occurs following envenoming by a number of carybdeid jellyfish species *characterised by severe hypertension, tachycardia, back pain, headache, muscle pains, chest and abdominal pain, *sweating, nausea and vomiting *infrequently, pulmonary oedema can occur *symptoms thought to be due to excess catecholamines - adrenaline, dopamine *treatment of symptoms only Spider *most widely distributed venomous creatures *responsible for most number of victims Redneck *only females are dangerous *antivenom introduced and no deaths since *related to American black widow *venom acts pre-synaptically to cause release and depletion of NA and ACh **results in patchy paralysis of NMJ and widespread release of catecholamines *symptoms - slow onset **sharp pain at the bite site **local sweating **nausea and vomiting **headache **hypertension¹ **tachycardia¹ ¹ adrenergic effects First aid *ice packs for pain relief *pressure immobilisation not recommended *CSL red-back antivenom (if systemic) Funnel Web *males are most dangerous *no deaths since introduction of antivenom *rapid onset of symptoms - pressure/immobilisation necessary immediately Phase 1 *autonomic storm - massive uncoordinated release of transmitters *acts directly on nerve fibresproducing spontaneous repetitive action potentials leading to uncoordinated muscle twitching *pain at bite site, muscle spasms, tachycardia, hypertension, nausea, vomiting, abdominal pain, salivation and lachrymation, death due to pulmonary oedema Phase 2 *phase 1 stops, refractory hypotension, cessation of breathing and cardiac arrest